The goal of this project is to determine the significance of phosphatidylinositol (PI) metabolism in specific cell types important in the mediation of inflammatory and immune responses. Experimentation will involve four established and pertinent in vitro models: lymphocyte transformation, IgE-mediated histamine release from leukocytes, polymorphonuclear leukocyte phagocytosis and lymphocyte-mediated cytotoxicity. The effect of PI metabolites, e.g., cyclic inositol phosphate and inositol, on these systems will be determined and the effects of agents already known to influence these processes on PI metabolism will be studied. It is known that mitogens and phagocytic stimuli cause increased PI metabolism in lymphocytes and polymorphonuclear leukocytes respectively. An additional aim will be to determine if antigen and anti-IgE have this effect in basophils. A recent study from my laboratory has established that colchicine, a drug which disrupts microtubules and inhibits many inflammatory processes, also inhibits PI turnover in lymphocytes. Experiments will be done to determine the mechanism whereby colchicine inhibits inflammatory and immune responses. It is anticipated that the present studies will establish a role for PI metabolites either as initiators or modulators of the inflammatory processes under consideration. The proposed work should also provide a clearer understanding of the processes themselves and may define new loci for possible pharmacological control of inflammation in disease states.